Table 1.

Vitamins, oligoelements, flavonoids, and polyphenols: their antiviral, anti-inflammatory, and antioxidant activities and their preventive effects against viral infections and their long-term consequences.

Componet	Mechanism of Action	References
Vitamin D	-immune modulating effect, reduces the frequency of respiratory infections	[51]
	-antioxidant and NrF2 stimulating effects thus increasing the synthesis of anti-inflammatory proteins	[51,142,143,144]
	-increases resistance to COVID-19 infection	[54]
	-reduces mortality related to COVID-19 complications	[27,55]
	-increases phagocytosis and killing of Streptococcus pneumoniae	[145]
	-reduces thrombosis risk	[146]
Vitamin E	-reduces oxidative stress	[147]
	-improves immune functions	[147]
Zinc	-anti-inflammatory effects inhibiting NF- κB activation	[148]
	-reduces oxidative stress induced damages on epithelial cells	[148]
	-improves immune defenses by:	[149]
	(1)increasing NK and cytotoxic CD8+ cell activity	[150]
	(2)reducing viral replication	[151]
	(3)reducing respiratory tract infections	[151]
	-suggested favorable effects on COVID-19:	[149]
	(1)improved cilia morphology and increased ciliary beat frequency	[149]
	(2)up-regulation of tight junction proteins ZO-1 and claudin-1with increased epithelial barrier effect	[149]
	(3)inhibition of RNA dependent polymerase—an essential enzyme for viral replication	[149]
	(4)up-regulation of IFNα production and up-regulation of antiviral proteins (RNaseL and PKR) known to degrade viral RNA and inhibit its translation	[149]
	(5)anti-inflammatory activity through inhibition of NF-κB signalin, g resulting in down-regulation of proinflammatory cytokine production	[149]
	(6)inhibition of S. pneumoniae growth through modulation of bacterial Mn (II) homeostasis	[149]
	-supplemented in daily doses of 7 mg in the elderly reduces pneumonia mortality by 39% and all-cause mortality by 53%	[152]
	-supplemented in adults reduces duration of symptoms of respiratory infections by 47%	[153]
	-its deficiency is associated with poor COVID-19 outcomes	[28,29]
Selenium	-in association with vitamin E, reduces ROS formation	[154]
	-promotes cell-mediated (TH1) immune response	[155,156,157]
	-enhances the function of cytotoxic effector cells, maintains T cell maturation and functions, as well as T cell-dependent antibody production and reduces viral replication and mutations	[30,83,92,154,157,158,159,160,161]
	-reduces platelets aggregation and consequent thrombosis	[98,162]
Magnesium	-reduces SARS-CoV-2 mortality	[31,32,34]
	-reduces:
	(1)low grade persistent inflammation	[31,163]
	(2)endothelial dysfunction	[31,163]
	(3)thrombosis risk	[163]
	(4)cytokine storm	[164]
	(5)collagen deposition and tissue fibrosis	[165]
	-if used in patients with COVID-19, reduces the need of oxygen therapy and intensive care unit admission	[46]
	-reduces the risk of cardiac arrhythmias	[166]
Flavonoids and polyphenols: quercetin, resveratrol, sulforaphane	-anti-inflammatory activity through activation of Nrf2 pathway and stimulated production of anti-inflammatory enzymes and proteins	[116]
	-anti-inflammatory activity through inhibition of NF-κB signaling, resulting in down-regulation of proinflammatory cytokine production	[116]
	-antiviral effect by conformational isomerism and molecular docking with the enzymes used by virus for replication	[118,119,121,167,168,169,170]
	-reduces the risk of thrombosis by anti-platelets aggregation activity	[123,124,170,171,172]
	-reduces the risk of cerebrovascular pathology	[125]
	-reduces the risk of pulmonary fibrosis by inhibiting leukocyte proteases	[143]
Curcumin	-reduces symptoms, inflammatory responses, and mortality in patients with COVID-19	[127,128,173]
	-reduces platelets activation and coagulation throughout multiple pathways	[172,174]
Sulforaphane	-probably responsible for death rate reduction for COVID-19	[25,131]
	-improve Nrf2 signal, mitochondrial ATP synthesis, improves glucose and fat metabolism, anti-inflammatory effect through JNK/AP-1/NF-κB inhibition and Nrf2/HO-1 activation	[132]
	-reduces the risk of thrombosis by anti-platelets aggregation activity	[123]